The country is making huge investments in health Information technology (HIT), with the belief that HIT will be a key tool to enable healthcare to begin to cross the quality chasm. Substantial research now demonstrates that in specific best-case situations, that HIT can be used to dramatically improve the safety and quality of prescribing, while reducing its costs. As a result, the intersection between therapeutics and HIT represents be a central driver of whether or not the nation actually receives the value expected to accrue from its HIT investment. Unfortunately, the outcome remains uncertain. Specific frontiers include how to do more effective post-marketing surveillance, how to use decision support to improve therapeutics in chronic disease management, how to ensure that HIT interventions cause a minimal number of new errors, how to smooth transitions for patients, how the onset of clinical data exchange will affect the equation, and what decision support can be broadly implemented. In this proposal, we describe the following six projects, which address these issues, and all the key priorities in the request for applications. 1) An evaluation of the impact of using telephony to ask outpatients known from the electronic health record (EHR) data to have been prescribed specific medications whether or not they are experiencing specific adverse effects related to those medications. 2) Evaluation of the impact of clinical decision support and automated telephone outreach on antihypertensive and lipid-lowering therapy in ambulatory care. 3) Qualitative evaluation of new errors created when electronic prescribing is implemented. 4) Evaluation of the impact of implementation of a post-discharge ambulatory medication reconciliation intervention. 5) Evaluation in New York among 6 Regional Health Information Organizations of their effects on medication safety. 6) Development of AMIA's ONCHIT-sponsored Clinical Decision Support Roadmap with identification of a set of clinical decision support rules which can be used in multiple settings. These results should both help in assessing how current HIT-related interventions can be rolled out broadly, and also break new ground. In addition, we will build and bolster educational tools and programs to assist with therapeutics and HIT.